THRB p.Glu449Ter
c.1345G>T · rs1553609157 · VCV439309
Likely pathogenic
Multiple submitters
Classification
Likely pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
2
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a LoF-intolerant gene |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (11 of 11) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | Δ0.27 | donor gain · deltas |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 2.1, phastCons 1 |
| Overall | ||
| CADD | 44.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- THRB
- Protein
- p.Glu449Ter
- Coding
- c.1345G>T
- MANE Select
- NM_001354712
- dbSNP
- rs1553609157
- Type
- single nucleotide variant
- Location
- chr3:24122925 (GRCh38)
- Gene constraint
- LOEUF 0.43 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 80.24 · 34 PDB
- Residue 449
- the nr lbd domain; the 'interaction with nr2f6' region; an α-helix
Similar variants
- THRB p.Ala268Gly Pathogenic/Likely pathogenic ★★ same condition
- THRB p.Ala317Thr Pathogenic ★★ same condition
- THRB p.Arg316His Pathogenic ★★ same condition
- THRB p.Arg320Cys Pathogenic ★★ same condition
- THRB p.Arg320His Pathogenic/Likely pathogenic ★★ same condition
- THRB p.Arg338Trp Pathogenic ★★ same condition
- THRB p.Arg383His Pathogenic/Likely pathogenic ★★ same condition
- THRB p.Arg429Gln Pathogenic/Likely pathogenic ★★ same condition
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/thrb-p-glu449ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown